What does the research say?
In a review of 16 pain studies that used pharmaceutical-grade pure CBD, CBD was not superior to placebo in 15 of them; problems with the content and purity of the products also stood out. In a study that followed 200 people with fibromyalgia for 24 weeks, pain went down slightly more in the placebo group than in the CBD group.
In a study of 102 women with chronic pelvic pain due to endometriosis, a CBD-rich oil was increased up to 150 mg a day over 10 weeks; pain went down to a similar degree in both groups. The study was stopped early because it became clear that no difference would emerge and mild side effects were more common in the CBD group. In 54 people with muscle pain in the jaw joint area, 20 mg of CBD oil a day for 3 months also did not change pain differently from placebo. There are two more small studies in endometriosis: the results of a CBD study that enrolled 10 women and was stopped early exist only in its registry entry, and another study that tested CBD oil and THC products could not recruit enough participants; no conclusions can be drawn from either.
Lowering the dose of opioid painkillers is a separate question, and the evidence for it is weaker (very low certainty). In well-designed studies that added a cannabinoid to an opioid, the opioid dose was kept fixed, and in the analysis that pooled these studies, opioid use did not change. In the only randomized study that tested this question directly, among 87 adults with chronic pain who were taking opioids, opioid dose and pain did not differ between those who started using cannabis right away and those who waited 24 weeks; symptoms of anxiety and cannabis use disorder were somewhat more common in the cannabis group (results only in the ClinicalTrials.gov registry, no peer-reviewed publication). Most studies reporting that opioid use went down are observational studies based on patients' own reports, with no comparison group. In large studies that used prescription records or a comparison group, the results are inconsistent: opioid use did not go down in a study in Australia that followed 1514 people taking opioids for 4 years, nor in a US registry study of 5296 people; two studies in New York saw a small decrease; in Canada, among older patients, starting long-term opioids was more common after a cannabis prescription. Recent studies have also not confirmed that opioid problems decreased in states where cannabis was legalized. In a study comparing a THC-dominant extract with opioids in chronic low back pain (not blinded, run by the manufacturer), constipation was less common; the difference in pain, however, was small and was not significant in the analysis carried out in the pre-specified order. In an analysis that indirectly compared cannabis studies with opioid studies, the effect on pain was similar and fewer people stopped cannabis because of side effects (low certainty); in a large registry study in Canada comparing people who started nabilone with people who started opioids, falls, fractures and deaths were less common, while mental health problems related to substance use were more common. In a small study of patients taking methadone, a high dose of CBD lowered the pain threshold, meaning it increased sensitivity to pain.
Cannabis products containing THC and taken by mouth brought a small or very small improvement in pain (moderate certainty); according to the most recent review from 2026, these products may reduce pain by between half a point and one point on a 10-point scale (low or moderate certainty), but they clearly increase dizziness, drowsiness and nausea. In chronic low back pain, a THC-dominant plant extract gave 0.6 points more relief than placebo at 12 weeks; in the randomized phase that looked at the effect of stopping the medicine, the difference was not significant. This study was run by the product's manufacturer. One expert guideline (BMJ) gives a weak recommendation for trying these products when standard treatment has not been enough; the International Association for the Study of Pain (IASP), however, does not support the general use of cannabis products for pain; the UK's national guideline (NICE) also does not recommend THC-containing products for chronic pain and recommends CBD only in clinical trials. The American College of Physicians (ACP, 2025) recommends that physicians discuss the benefits and harms with the patient; explain that in young adults and adolescents, in people with a substance use disorder or serious mental illness, and in frail patients at risk of falls, the harms most likely outweigh the benefits; and advise against inhaled cannabis. A guideline prepared in Canada, however, recommends cannabis-based medicines for chronic pain with a strong recommendation and writes that the strongest evidence is for THC-containing products, not for CBD; but this guideline also takes studies without a comparison group into account, its search ends in 2019, a cannabis company gave financial support for its preparation, and some of its authors have ties to cannabis companies. It has also been found that some publications in this field describe the results more favorably than they really are.
In small, placebo-controlled studies with THC-containing products in chronic abdominal pain (chronic pancreatitis) and sickle cell disease, pain did not go down clearly differently from placebo. The small study in patients on hemodialysis was designed only to measure safety; pain was not compared statistically between the groups. Because these studies were done with few people over a short time, they are not conclusive, but they did not show a clear benefit either.
Patient registries and large studies without a control group report that pain decreases over time in people who start cannabis (for example, 3744 patients in the UK). In a study in Israel that followed 1000 patients with chronic low back pain who started cannabis for 10 years, pain and opioid dose also fell very markedly among those who completed follow-up; the authors themselves write that this effect is much larger than in placebo-controlled studies and that the biases of this kind of study play a part in it. These studies have no comparison group, most patients drop out of follow-up, and some registries belong to companies that prescribe the products; so it is not known how much of the improvement comes from the product. A registry in Germany reported better results in older patients with products described as 'CBD-dominant,' but the people in this group were also taking about 16 mg of THC a day on average. Reviews that pooled studies of this kind rated the evidence as very low certainty.
Strength of evidence: ●●●○ Moderate evidence. Finding: No effect found. What does this mean?
Ongoing research on this topic
Trials testing CBD for this topic on ClinicalTrials.gov: 19 under way (13 recruiting); results are awaited from 8 that ended in the last two years. A trial being under way does not show that CBD works.
- NCT05052541: Phase 3, recruiting, target 157 participants
- NCT07552974: Phase 2/3, not yet recruiting, target 100 participants
- NCT06213233: Phase 2, recruiting, target 468 participants
Registries in other countries also list 3 recruiting trials on this topic: other registries.
Possible side effects and drug interactions
In the fibromyalgia study, the side effects of pure CBD were mostly mild and similar to placebo. Dizziness, drowsiness and nausea were more common with THC-containing products. In observational studies following long-term use, about a quarter of users reported side effects; serious side effects occurred in fewer than 1 in 20 people. In two studies where cannabis use was assigned by lottery, symptoms of cannabis use disorder increased. Studies in healthy adults also found that liver enzymes rose in some people.
CBD can slow down how the body breaks down some medicines. Drowsiness may increase when it is combined with opioids, gabapentin, pregabalin, sedatives and alcohol. Caution is needed with blood thinners such as warfarin and clopidogrel and with medicines that can put a strain on the liver, such as acetaminophen (paracetamol).
Interactions with medicines used for this condition
Interactions reported for these medicines in peer-reviewed publications and official prescribing information. A medicine that is not listed can still interact with CBD; tell your doctor about every medicine you take.
| Medicine | Importance | Warning | Source |
|---|---|---|---|
| Other opioids (morphine, oxycodone, fentanyl, tramadol, etc.), Methadone | Caution | Methadone and other opioids: In a child, a high methadone level was found and drowsiness developed while CBD was being used; two weeks after CBD was stopped, the level fell to less than half and the symptoms resolved. In small controlled studies with morphine and buprenorphine, no clear change in drug levels was seen; with a single intravenous dose of fentanyl, there was no respiratory depression. Drowsiness may increase together with opioids. Tell the doctor who manages your pain or addiction treatment. | PMID 32444381, PMID 41622700, PMID 41467610, PMID 25748562, FDA Epidiolex label §7.4 (05/2026) |
| Gabapentin (Gabateva, Neruda), Pregabalin (Lyrica) | Caution | Benzodiazepines, sleep medicines and sedatives: Drowsiness and sedation may increase together with CBD. Talk to your doctor before using them together. | DailyMed Epidiolex label 7.4, EMA Epidyolex SmPC 4.4 |
| Acetaminophen (paracetamol) | Caution | Acetaminophen and the liver: In a knee osteoarthritis study, liver enzyme elevations were more common in people taking 600 mg of CBD together with 3 g a day of acetaminophen (paracetamol) than with placebo (15 vs. 5 patients). Enzyme elevations were also seen in healthy adults at a lower CBD dose (5 mg/kg a day). If you take acetaminophen regularly, talk with your doctor about liver tests. | PMID 38033459, PMID 40622698 |
| Tizanidine | Caution | Theophylline, tizanidine: CBD can raise the blood levels of these medicines; the prescribing information for approved CBD recommends considering a dose reduction. The tizanidine prescribing information itself asks that it not be combined with weak CYP1A2 inhibitors such as CBD; low blood pressure, a slowed heart rate or excessive drowsiness may occur. Tell your doctor. | FDA Epidiolex label §7.2 (05/2026), EMA Epidyolex SmPC 4.5, PMID 33951339, Tizanidine prescribing information §7.2, dailymed.nlm.nih.gov |
| NSAIDs (ibuprofen, naproxen, celecoxib, etc.) | Information | NSAID pain relievers: There is no documented meaningful interaction between CBD and these pain relievers; there are no direct studies either. The bleeding and kidney risks come from the NSAID itself. | FDA Epidiolex label §12.3 (05/2026), Celecoxib prescribing information §7, dailymed.nlm.nih.gov |
To check interactions with the medicines you take: CBD drug interaction checker.
How was CBD used in studies?
In pain studies, pure CBD was used across a very wide range, from 6 mg to 1600 mg (study dose; not a personal recommendation). In the fibromyalgia study, 50 mg a day was given (study dose; not a personal recommendation). In most studies the dose was kept fixed, and no dose showed a consistent benefit.
In chronic pain studies with THC-containing products, doses were started low and raised slowly every few days; for example, in the chronic low back pain studies the dose unit was 2.5 mg of THC, up to 13 units a day were allowed, and participants stayed at 7–8 units on average (study dose; not a personal recommendation). Side effects were seen most often during the dose-increase period.
Study details (for health professionals)
In chronic pain, CBD was not superior to placebo in 15 of 16 RCTs that used pharmaceutical-grade pure CBD (Moore 2024). In the fibromyalgia RCT (50 mg/day, 24 weeks), placebo did better than CBD. In chronic pelvic pain due to endometriosis, a CBD-rich oil (up to 150 mg/day, 10 weeks, 102 people) was no better than placebo, and the study was stopped at an interim analysis; in jaw joint muscle pain, 20 mg/day of CBD oil (3 months, 54 people) also did not change pain. No RCT has been reported showing an opioid-reducing effect of pure CBD in chronic pain. Oral medical cannabis containing THC gave a small to very small improvement in pain (moderate certainty), and the BMJ guideline made this a weak recommendation. IASP (2021) does not support the general use of cannabinoids for pain. According to the 2026 update from the US Agency for Healthcare Research and Quality (AHRQ) (25 RCTs, 2303 people), oral THC and balanced THC:CBD products may reduce pain slightly (low or moderate certainty), while CBD-dominant products may not; according to Stockings 2018, 24 people need to be treated for one person to get meaningful relief, and 1 in every 6 people has an additional side effect. The UK's national guideline (NICE 2019) does not recommend THC-containing products for chronic pain and recommends CBD only in clinical trials; the American College of Physicians (ACP 2025) says that in young adults and adolescents, in people with a substance use disorder or serious mental illness, and in frail patients, the harms most likely outweigh the benefits, and that inhaled cannabis should not be used. A clinical guideline prepared in Canada (Bell 2024), however, summarizes the evidence as 'at least a moderate benefit in most studies' and recommends cannabinoid-based medicines for chronic pain at the level of 'strong recommendation, moderate-quality evidence'; the guideline itself also writes that the strongest evidence is for THC-containing products, not for CBD. This guideline's search ends in 2019, it also counts uncontrolled studies, a cannabis company took part in its funding, and 7 of its 20 authors reported ties to cannabis companies; meta-analyses that pool only placebo-controlled studies, on the other hand, find the benefit small or very small. Small THC RCTs in chronic abdominal pain and sickle cell disease found no difference from placebo; in the safety study in hemodialysis patients, pain was not compared statistically. On the opioid reduction question, opioid dose did not fall in RCTs (Noori 2021, very low certainty); in the only study where cannabis use was assigned by lottery to 87 adults with chronic pain taking opioids, opioid dose and pain at 24 weeks also did not differ from the waiting group (results only in the ClinicalTrials.gov registry). While uncontrolled studies based on patients' own reports describe a clear decrease in opioid use (in the observational studies pooled by Nielsen 2022, the pooled proportion who said they had lowered their dose was 85%; in an uncontrolled series of 1000 patients with chronic low back pain followed for 10 years in Israel, opioid dose fell by 90% among those who completed follow-up, and the authors themselves write that observational bias plays a part in this, Khatib 2026), studies using prescription records or a comparison group show no effect (Campbell 2018, Goedel 2022), a small effect (Nguyen 2023, Slawek 2026) or an effect in the opposite direction (Fontaine 2026: starting long-term opioids was more common in older adults). In a network meta-analysis that indirectly compared cannabis and opioid studies, no difference in pain was seen (low certainty), and fewer people stopped cannabis because of side effects (Jeddi 2024); in a large registry study comparing people who started nabilone with those who started opioids, falls, fractures and deaths were less common, while mental health problems related to substance use were more common (Vozoris 2024). In healthy volunteers, it is inconsistent whether THC increases the painkilling effect of opioids; THC may increase the abuse-related effects of opioids (Nielsen 2022). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 20 randomized controlled trials with cannabinoids on this topic were found (8 with CBD alone; 2 laboratory studies in healthy volunteers done together with an opioid; 3 with results only in the ClinicalTrials.gov registry), along with 11 systematic reviews, 1 publication bias analysis, 5 guidelines or position statements and 12 observational or uncontrolled studies; all are in the table below. Cochrane has no review specific to general chronic pain. Laboratory studies in healthy volunteers that tested CBD together with an opioid are listed one by one in the table; the 5 laboratory studies that tested THC together with an opioid were not listed individually but are summarized through the Nielsen 2022 row. The many small patient registries and uncontrolled studies were also not listed individually; they are summarized through reviews (Nielsen 2022, Noori 2021, Bialas 2022, Zeraatkar 2022).
Evidence assessment: Moderate (no benefit seen with pure CBD; placebo did better in the fibromyalgia RCT); opioid reduction: very low certainty (opioid dose did not fall in RCTs)
CBD alone
Pure CBD was not found to be better than placebo in chronic pain (Moore 2024: 15 of 16 RCTs; AHRQ living review: no difference in pain in 4 RCTs of oral pure CBD, moderate certainty), and an opioid-reducing effect has not been shown in RCTs; no conclusions can be drawn from two small CBD studies in patients taking opioids (an RCT that finished with 6 people and an uncontrolled cohort of 97 people).
Products containing THC
Oral THC-containing cannabinoids give a small improvement in pain (Wang 2021: −0.50 cm VAS; AHRQ 2026: oral THC −0.78, THC:CBD oral spray −0.54 points/10), with increased dizziness, drowsiness and nausea; in chronic low back pain, a THC-dominant full-spectrum extract gave −0.6 NRS versus placebo. In the open-label manufacturer study comparing the same extract with opioids, constipation was less common; the difference in pain was small (0.34 points) and not significant in the confirmatory analysis carried out in the pre-specified order. Small RCTs in chronic abdominal pain and sickle cell disease found no difference from placebo (in the safety study in hemodialysis patients, pain was not compared statistically between groups); NICE (2019) does not recommend them for chronic pain.
Evidence: Moderate certainty, small to very small effect (Wang 2021); AHRQ 2026: low–moderate certainty, small effect; BMJ guideline weak recommendation, NICE (2019) does not recommend
Dose range in studies
Pure CBD in pain RCTs 6–1600 mg (Moore 2024); fibromyalgia 50 mg/day; endometriosis 10–150 mg/day; jaw pain 20 mg/day; 50–1200 mg single doses in laboratory opioid interaction studies; 600 mg/day in patients with radicular pain taking opioids (6 people). In studies of THC-containing or THC-like products: nabilone (a synthetic THC-like cannabinoid) 0.25–1 mg/day, dronabinol 10–20 mg single dose, purified THC up to 24 mg/day (abdominal pain), THC-dominant extract with a dose unit of 2.5 mg THC and at most 13 units a day (low back pain) (study doses; not a personal recommendation)
Starting dose and titration
Schedules used in the studies (not a personal recommendation): in most CBD studies the dose was fixed from the start; in the endometriosis study, the CBD-rich oil was raised from 10 mg/day in weekly steps to 150 mg/day by week 9. In studies of THC-containing products, the dose was increased little by little every few days (e.g., every 3 days in the low back pain study), and side effects were seen most often during this increase period
These are doses researchers gave under medical supervision; they are not a recommended dose for you. "mg/kg/day" means milligrams per kilogram of body weight per day.
| Study | Participants | Product | Dose and titration | Duration | Result | Source |
|---|---|---|---|---|---|---|
| Rasmussen 2026 Double-blind, placebo-controlled, single-center RCT | 200 (100/100) Fibromyalgia | Plant-derived CBD tablets (CBD as the only active ingredient; THC content not reported in the abstract or the registry) | 50 mg/day According to the registry plan, it was to start at 10 mg/day and be increased every 3 days to reach 50 mg/day in 2 weeks (the full text of the article could not be read; the schedule actually used could not be verified) | 24 weeks | Change in pain −0.4 with CBD, −1.1 with placebo; difference in favor of placebo (−0.7; p=0.0028) Side effects: Mostly mild; similar between groups | PMID 40846590, doi:10.1016/j.ard.2025.07.008, NCT04729179, no results in the registry) |
| Bergeria 2025 Within-subject, double-blind, double-dummy RCT | 31 Healthy volunteers, laboratory pain model | Oral CBD + 4 mg hydromorphone | 50–200 mg Fixed-dose conditions | Single sessions | Opioid analgesia increased on some acute pain measures; no effect in chronic pain models Side effects: At 200 mg, 'bad effects' and adverse events increased; CBD reduced psychomotor impairment | PMID 40839659, doi:10.1097/j.pain.0000000000003561 |
| Costa 2026 Crossover, double-blind, placebo-controlled RCT | 23 Opioid use disorder on methadone treatment + chronic pain | Oral CBD | 400–1200 mg Fixed-dose arms | Single-dose sessions | Before methadone, descending pain inhibition increased with dose; after methadone, 1200 mg lowered the pain threshold (worsening); opioid craving did not change. A single-dose study using laboratory pain tests. In the registry (NCT04587791), the primary outcomes are safety, abuse potential and cognition, with pain measures secondary; the article presents pain modulation measures as the primary outcome. The manufacturer supplied the CBD and placebo; 1 of the 6 authors reported drug support and consulting fees from pharmaceutical companies Side effects: Cognition preserved; safety reported as 'favorable' | PMID 42162267, doi:10.1038/s41386-026-02443-w, NCT04587791, PMID 41496743, 7 people with chronic pain on methadone or buprenorphine, 400–1200 mg CBD, no significant main effect on pain sensitivity, an interaction with medication type, CBD well tolerated) |
| Anelli 2026 (DREAMLAND) Single-center, triple-blind, placebo-controlled parallel RCT; stopped at an interim analysis | 102 (51/51) Women with endometriosis who had had surgery, were on hormone therapy and whose symptoms had returned (chronic pelvic pain) | CBD-rich extract oil (THC content not in the abstract) | From 10 mg/day to 150 mg/day by week 9, then tapered; twice a day Weekly increases: 10 mg/day (week 1) → 150 mg/day (week 9), then tapered off | 10 weeks | A ≥50% reduction in pain in about 40% of both groups; pain at the end of treatment 41.6 mm with CBD, 36.8 mm with placebo (difference not significant); stopped at the interim analysis because of lack of effect and more side effects Side effects: Mild side effects more common with CBD (gastrointestinal complaints, a sense of weight change); no serious adverse events | PMID 42261989, doi:10.1177/25785125251413989 |
| Reeve 2026 Single-center, placebo-controlled RCT (2:1 randomization); in the registry only participants were blinded, according to the publication assessors were also blinded | 62 registered and randomized; 54 analyzed (35 CBD / 19 placebo) Myofascial pain in the jaw joint area (US) | Sublingual CBD oil (20 mg/mL); placebo hemp seed oil | 20 mg/day (1 mL sublingual) | 3 months | Jaw pain did not differ between groups at months 1, 2 and 3 (p>0.56); jaw function improved in both groups. 8 of 62 people were not included in the analysis (5 did not return for follow-up, 3 were excluded because of a diagnostic error). The dose was low (the authors also note this); the product and funding were provided by a CBD oil manufacturer Side effects: Mild side effects in 4/38 with CBD (10.5%; most common headache), 4/19 with placebo (21%) | PMID 42016900, doi:10.1159/000551040, NCT04298554, the registered primary outcome was change in pain from baseline at weeks 3, 7 and 11, the published primary outcome was pain at month 1, no difference under either definition, no results in the registry), PMC13095194, the same study is also in the site's jaw joint and teeth clenching table |
| Manini 2015 Crossover, double-blind, placebo-controlled | 17 (CBD 400 mg: 6, 800 mg: 6, placebo: 5) Opioid-experienced healthy volunteers | Oral CBD + IV fentanyl | 400–800 mg | Single dose | CBD did not increase the side effects of fentanyl Side effects: No respiratory depression or cardiovascular complications | PMID 25748562, doi:10.1097/ADM.0000000000000118 |
| Karst 2025 (VER-01, placebo-controlled) Phase 3, double-blind, placebo-controlled RCT | 820 Chronic low back pain | Full-spectrum C. sativa extract, oral; 2.5 mg THC, 0.1 mg CBG, 0.02 mg CBD per dose unit | Individualized; at most 13 dose units/day (2.5 mg THC per unit) Increased by one unit morning and evening every 3 days | 12 weeks (+ extension) | In the 12-week double-blind period, pain fell by 1.9 points with VER-01; difference versus placebo −0.6 NRS (95% CI −0.9 to −0.3; p < 0.001). The difference was larger in those with a neuropathic component (−1.5). In the open-label extension, pain fell further (−2.9; no control group); in the randomized withdrawal period, the primary outcome (time to treatment failure) was not significant (HR 0.75; 95% CI 0.44–1.27). The study was funded by the product's manufacturer (Vertanical), which took part in its design; 2 of the 6 authors received consulting fees from the company or research support to their institution, and 1 worked at the firm the company hired for statistics Side effects: Adverse events 83.3% versus 67.3%; discontinuation due to side effects 17.3% versus 3.5% (most common dizziness, drowsiness, nausea); no signs of dependence or withdrawal | PMID 41023483, doi:10.1038/s41591-025-03977-0, NCT04940741, the RCT comparing the same product with opioids is a separate row in the table (Meissner 2025) |
| Moore 2024 (J Pain) Systematic review (pure CBD pain RCTs after IASP) | 16 studies Various types of pain | Pharmaceutical-grade CBD | 6–1600 mg | No superiority over placebo in 15 of 16 studies; product content and purity problematic; signal of liver toxicity | PMID 37863344, doi:10.1016/j.jpain.2023.10.009 | |
| Fisher 2021 (IASP systematic review) Systematic review (RCTs; IASP task force; GRADE) | 36 RCTs, 7217 people All types of pain | Cannabinoids, cannabis, cannabis-based medicines | Benefit signal only with short-term cannabis and with nabiximols for >7 days (very low quality); 81% of subgroups negative; no pure CBD RCT; the evidence neither supports nor refutes efficacy | PMID 32804836, doi:10.1097/j.pain.0000000000001929 | ||
| Wang 2021 Systematic review and meta-analysis (32 RCTs) | 5174 Chronic non-cancer and cancer pain | Oral/topical cannabinoids | Pain −0.50 cm VAS (moderate certainty): small effect Side effects: Increased risk of dizziness, drowsiness and nausea | PMID 34497047, doi:10.1136/bmj.n1034 | ||
| Busse 2021 (BMJ Rapid Recommendation) Clinical practice guideline | Chronic pain | Oral cannabinoids | Weak recommendation for a trial of oral cannabinoids if standard treatment is inadequate; shared decision-making required | PMID 34497062, doi:10.1136/bmj.n2040 | ||
| Nielsen 2022 Systematic review and meta-analysis (preclinical + clinical) | Opioid reduction | Cannabinoids | No opioid-reducing effect was shown in RCTs (opioid dose difference in 4 RCTs in cancer pain −3.8 mg; 95% CI −10.97 to 3.37); opioid reduction was reported only in observational studies (prone to bias; pooled proportion reporting a lower dose 85%, stopping 39%). In 5 laboratory studies in healthy volunteers, adding a cannabinoid increased pain in two, reduced it in two, and in one reduced only the unpleasantness of pain; in three, it could increase the abuse potential of the opioid. In animals, the morphine dose needed for the same painkilling effect was 3.5 times lower with THC | PMID 35459926, doi:10.1038/s41386-022-01322-4 | ||
| Moore 2024 (Pain) Publication bias analysis | Cannabinoid–pain publications | Moderate–severe narrative bias ('spin') in 24% of RCTs and 17% of reviews; the bias always favored the product | PMID 38227560, doi:10.1097/j.pain.0000000000003140 | |||
| IASP 2021 position statement Task force position statement | Pain | Cannabinoids | Does not support the general use of cannabinoids for pain; calls for more research, product standards and regulation | PMID 33729207, doi:10.1097/j.pain.0000000000002265, www.iasp-pain.org | ||
| Notcutt 2004 Open-label run-in period followed by randomized, double-blind, placebo-controlled crossover 'N-of-1' (single-patient) trials | 34 patients (each patient their own control) Patients with chronic pain, mostly neuropathic | Three cannabis extracts sprayed under the tongue: THC, CBD and 1:1 THC:CBD | Adjusted for each patient; dose requirements varied widely (figures not in the abstract) During the open-label period, each patient found their own dose | 12 weeks | Extracts containing THC reduced symptoms the most; the CBD-only extract lagged behind them (no numerical comparison in the abstract). Because these were single-patient trials, results were assessed patient by patient rather than between groups; a small, old, early-experience study Side effects: Side effects were common; according to the authors, similar to those of other psychoactive medicines used for pain and generally acceptable | PMID 15096238, doi:10.1111/j.1365-2044.2004.03674.x |
| Pinsger 2006 Double-blind, placebo-controlled crossover pilot RCT (2 × 4-week drug periods) followed by a 16-week period in which patients chose their own medicine | 30 (all analyzed) Treatment-resistant chronic pain related to the musculoskeletal system (mostly spinal pain) | Nabilone capsules (a synthetic THC-like cannabinoid), added to standard treatment | 0.25–1 mg/day (1–4 capsules a day) Patients adjusted the dose themselves between 1 and 4 capsules a day | 14-week crossover period + 16-week choice period | During nabilone periods, current spinal pain fell by 0.6 points on the VAS, with no change on placebo (0.0; medians; p = 0.006); there is also a difference in favor of nabilone in mean spinal pain over the last 4 weeks (0.9 versus 0.5) and in headache (1.0 versus 0.2), but the abstract gives no p value for these two. In the choice period, patients used nabilone on 89% of days and placebo on 11% (p = 0.003). Small pilot study; only the English abstract of the German-language article was read Side effects: Not reported (in the abstract) | PMID 16855921, doi:10.1007/s00508-006-0611-4 |
| Narang 2008 Two phases: phase 1 randomized, double-blind, placebo-controlled, single-dose crossover RCT (3 visits × 8 hours); phase 2 open-label extension with dose adjustment | 30 Patients with chronic non-cancer pain whose pain persisted despite a stable dose of opioids (US) | Dronabinol capsules (synthetic THC), added to opioids | Phase 1: 10 mg or 20 mg single dose; phase 2: adjusted dose Open-label dose adjustment in phase 2 | Single-dose sessions + open-label extension (duration not in the abstract) | As a single dose, dronabinol reduced pain intensity and increased satisfaction compared with placebo; no difference between 10 and 20 mg. In the open-label extension, pain fell from baseline (no control group). The opioid dose was not changed in this study: the study examined the added painkilling effect on top of opioids, not opioid reduction. In the second publication from the same trial, a single dose of dronabinol produced mind-altering effects at a level similar to smoked marijuana. According to the registry, the drug's manufacturer at the time (Solvay) supported the study Side effects: Side effects increased with dose | PMID 18088560, doi:10.1016/j.jpain.2007.10.018, NCT00153192, PMID 24281276, 10 and 20 mg dronabinol increased mind-altering effects more than placebo on 4 of 5 subscales, with peak effects similar to smoked marijuana) |
| de Vries 2016 Randomized, double-blind, double-dummy, active placebo-controlled, single-dose crossover RCT | 24 Chronic abdominal pain due to chronic pancreatitis (Netherlands; later divided into subgroups of opioid users and non-users) | Oral purified THC tablet; comparison diazepam (active placebo) | 8 mg THC single dose (diazepam 5 or 10 mg) | Single dose (2 sessions) | A single dose of THC did not reduce pain differently from diazepam (no difference in VAS change). With THC, feelings of anxiety and heart rate increased compared with diazepam; no difference in alertness, mood and balance Side effects: Most common were drowsiness, dry mouth, dizziness and euphoric mood; all mild or moderate | PMID 26505163, doi:10.1111/bcp.12811, NCT01318369 |
| de Vries 2017 Phase 2, randomized, double-blind, placebo-controlled parallel RCT | 65 randomized Chronic abdominal pain lasting at least 3 months, after surgery or due to chronic pancreatitis (Netherlands) | Oral purified THC tablets, added to current pain medicines | 3 × 3 mg for 5 days, 3 × 5 mg for 5 days, then 3 × 8 mg (24 mg/day) From 3 × 3 mg to 3 × 8 mg over 10 days | 50–52 days | No difference between groups in the primary outcome (mean diary VAS pain, days 50–52) (p = 0.901): pain fell by 1.6 points (40%) with THC and 1.9 points (37%) with placebo; no difference in secondary outcomes (pain, quality of life) either Side effects: Discontinuation due to side effects in 7 patients on THC and 2 on placebo; all possibly drug-related side effects were mild or moderate | PMID 27720917, doi:10.1016/j.cgh.2016.09.147, NCT01562483 |
| Abrams 2020 Pilot, randomized, double-blind, placebo-controlled crossover RCT (inpatient, 2 × 5 days) | 27 randomized; 23 completed and were analyzed Adults with sickle cell disease and chronic pain taking stable pain medicines (mostly opioids) (US) | Vaporized inhaled cannabis (4.4% THC, 4.9% CBD); placebo cannabis | 3 times a day (the contents of one cannabis cigarette, vaporized) | 2 × 5 days | The difference in pain (VAS, 0–100) ranged from −5.3 to −16.5 points across days in favor of cannabis, but was not significant on any day; no difference in pain interference with daily activities, walking, sleep and enjoyment of life; improvement only in pain interference with mood (p = 0.02). Opioid use was similar in the two periods. Publicly funded (NIH); one of the 9 authors (the first author) reported receiving fees from cannabis companies outside the study Side effects: No difference between groups in treatment-related side effects | PMID 32678452, doi:10.1001/jamanetworkopen.2020.10874, NCT01771731 |
| Kliuk-Ben Bassat 2023 Randomized, double-blind, three-arm crossover feasibility RCT (primary outcome safety) | 15 randomized; periods analyzed: whole-plant extract 7, purified product 5, placebo 9 Patients on hemodialysis with chronic pain (Israel; 87% men, mean age 64) | Sublingual oil, THC:CBD 1:6 (24.5 mg THC, 147 mg CBD per mL); two forms, whole-plant extract or purified; product and funding from a pharmaceutical company (BOL Pharma) | 3 drops = 2.5 mg THC + 15 mg CBD; started at 3 drops once a day and raised to at most 3 × 6 drops a day (15 mg THC + 90 mg CBD/day) To 3 × 3 drops a day in the first week, and if there were no side effects, to at most 3 × 6 drops; because of tolerability problems the protocol was changed to a slower start | 8 weeks per period (2 weeks apart) | Safety study; the authors write that they did not compare efficacy statistically between groups (few people and a feasibility design). Worst pain (BPI, 1–10) fell by 3.3 points with the whole-plant extract and 1.3 points with placebo, and rose by 0.3 with the purified product; average pain −1.9, −0.9 and +0.6. Liver enzymes did not change. The study was funded by the product's manufacturer; 4 of the 10 authors are current or former employees of the company Side effects: Side effects in 8 of 9 people with the whole-plant extract, all 6 people with the purified product, and 8 of 10 people with placebo; most common were drowsiness and dizziness. Serious adverse event considered drug-related by the investigator: hallucinations and rapid heart rate after an accidental overdose with the whole-plant extract. With the purified product, the drug was stopped in one patient because of a marked drop in blood pressure considered drug-related, and the dose-increase schedule was slowed; one patient died of sepsis during dose adjustment (unrelated to the drug according to the investigator) | PMID 37007688, doi:10.1093/ckj/sfac275 |
| Gilman 2022 Pragmatic RCT (getting a medical cannabis card immediately or after 12 weeks; 2:1 randomization; participants not blinded, only assessors blinded) | 269 randomized (173 immediate, 96 delayed); 186 analyzed (105 immediate, 81 delayed): 53 who did not get the card, 15 found to have cannabis use disorder at baseline and 15 who did not attend follow-up were not included in the analysis; pain analysis in 61 people who sought care for pain (37/24) Adults aged 18–65 seeking medical cannabis for pain, insomnia, or symptoms of anxiety or depression; daily cannabis users and people with cannabis use disorder were not enrolled (US, Boston) | Cannabis products chosen by participants themselves from a dispensary (THC and/or CBD) | Participant's choice (product, dose and frequency unrestricted) Participant's choice | 12 weeks | Among those seeking care for pain, no difference between groups in pain severity (BPI, 0–10) (mean difference 0; 95% CI −0.8 to 0.9; p = 0.93); baseline pain was low (2.8 and 3.9). No difference in anxiety and depression either; only the insomnia score improved. Symptoms of cannabis use disorder increased in those who got the card (0.28; 95% CI 0.15–0.40) Side effects: At 12 weeks, cannabis use disorder in 17.1% of those who got the card immediately and 8.6% of those who waited (adjusted OR 2.88; 95% CI 1.17–7.07) | PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, 12 weeks, cannabis use frequency rose in those who got the card, reported sleep quality was better on days of use, no improvement in pain or depressive symptoms) |
| Meissner 2025 (VER-01, comparison with opioids) Phase 3, multicenter, randomized, open-label (not blinded) parallel RCT; comparison: opioid | 384 randomized (192/192); 140 and 126 completed treatment Chronic nonspecific low back pain without adequate benefit from non-opioid painkillers (mean age 55) | VER-01: oral full-spectrum Cannabis sativa extract (THC-dominant; dose unit 2.5 mg THC); comparison: a marketed opioid chosen by the physician (mostly tramadol, tapentadol, tilidine) | VER-01 an average of ~7.5 dose units a day (about 19 mg THC); opioid group an average of 27–32 mg morphine equivalent/day 3-week dose adjustment | 3 weeks of dose adjustment + 24 weeks of treatment | Primary outcome constipation: with VER-01, the risk of constipation was a quarter of that with opioids (RR 0.25; 95% CI 0.09–0.69); laxative use 5.8% versus 17.2%. Superiority for pain was not shown: the first pain outcome tested in the pre-specified order (proportion with at least a 30% reduction in pain at week 27) was not significant; so the subsequent pain analyses are exploratory only. In these analyses, averaged over 6 months, pain fell by 2.50 points with VER-01 and 2.16 points with opioids (difference 0.34; 95% CI 0.00–0.67; p = 0.048): a borderline and small difference (the authors present this as 'superiority' in the abstract). There was no blinding, most people in the opioid group took a weak opioid at a low dose, and discontinuation was higher in the opioid group. The study was run and funded by the product's manufacturer (Vertanical); 3 of the 5 authors received consulting fees from the company or research support to their institution, and 1 worked at the firm the company hired for statistics Side effects: Side effects 73.0% versus 73.7%; most common with VER-01 were dizziness (22%), vertigo (15%) and dry mouth (11%), and with opioids constipation (23%) and nausea (13%); discontinuation due to side effects 12.7% versus 13.4%; no withdrawal symptoms were seen when VER-01 was stopped abruptly | PMID 41028525, doi:10.1007/s40122-025-00773-z, NCT05610813, EudraCT 2022-001358-41 |
| NCT04527003 (endometriosis, registry results) Randomized, double-blind, placebo-controlled three-arm pilot RCT; ended early because patients could not be recruited; no peer-reviewed publication | 12 enrolled; 10 randomized (4 placebo, 3 low dose, 3 high dose); primary analysis 7 people (4/2/1) Women with pain due to endometriosis; everyone also took norethindrone acetate (a progestin medicine) (US, Penn State Hershey) | Sublingual CBD extract (product source and THC content not stated in the registry); placebo | 10 mg/day or 20 mg/day | 8 weeks | Primary outcome (area under the curve of daily pain over 8 weeks): placebo 2254, low-dose CBD 2211, high-dose CBD 1042 (only 1 person); no statistical comparison in the registry. Because the groups are very small, no conclusion can be drawn Side effects: No serious adverse events; other side effects in 3 of 4 people on placebo, 2 of 3 on the low dose, and no one on the high dose | NCT04527003, 2025, no publication found in the October 2026 search) |
| Chesterman 2025 Three-arm, randomized, placebo-controlled feasibility RCT | 12 randomized (target 63); 4 completed, 7 withdrew, 1 lost to follow-up People with endometriosis (Australia) | 1) Vaporized inhaled dried flower with 16% THC + oral CBD oil (100 mg CBD per mL); 2) oral CBD oil alone; 3) placebo oil matched for taste and color | Not reported (in the abstract) | Not reported (in the abstract) | Feasibility was not achieved: only 12 of the targeted 63 people could be enrolled, and 4 finished the study; efficacy could not be assessed. According to the authors, the main reasons for failure were the requirement not to drive and the high withdrawal rate. Funded by a state government; an employee of the company that donated the study products (ANTG) and the manager of the pharmacy that dispensed the product are among the authors (2 of 17 authors), and one author received consulting fees from the same company in 2019–2022 Side effects: 10 side effects (8 possibly related to cannabis) and 2 serious adverse events (both unrelated to treatment) | PMID 41005282, doi:10.1016/j.ctcp.2025.102023 |
| NCT04760613 (CBD in opioid users, registry results) Phase 1/2, randomized, double-blind, placebo-controlled pilot RCT; no peer-reviewed publication | 14 enrolled; 6 started and finished (5 CBD, 1 placebo) Patients with chronic spine-related radicular pain (radiculopathy) taking a stable dose of opioids for at least 1 month, without opioid use disorder (US, New York University) | Oral CBD capsules (50 mg CBD per capsule; product source not stated in the registry); placebo | 600 mg/day | 2 weeks | Primary outcome (change in blood opioid level): mean +10.9 ng/mL (SD 14.4) in the CBD group, −11.4 in the single placebo patient; pain (BPI) fell by 1.5 points in the CBD group, and the placebo patient did not complete the questionnaire. Because the groups had 5 and 1 people, no comparison can be made; these data cannot tell whether CBD changed opioid levels or pain. Supported by NIDA Side effects: Drowsiness, nausea, diarrhea and headache in 2 each of the 5 people taking CBD; the only serious adverse event was in the placebo patient (kidney stone) | NCT04760613, 2024, no publication found in the October 2026 search) |
| NCT04827992 (cannabis in opioid users, registry results) Pragmatic, randomized, waitlist-controlled parallel study (only outcome assessors blinded); both groups attended a weekly opioid tapering support group for 24 weeks; no peer-reviewed publication | 87 randomized (42 cannabis, 45 waitlist); pain analysis 78 people (41/37) Adults with non-cancer chronic pain taking prescription opioids at a stable dose of at least 25 mg morphine equivalent a day who wanted to reduce their pain or opioid dose with cannabis (US, three academic centers) | Cannabis products chosen by participants themselves from commercial dispensaries (product type, dose and frequency unrestricted); comparison: waitlist group that agreed not to use cannabis for 24 weeks | Participant's choice (no dose information in the registry) Participant's choice | 24 weeks | No difference in either primary outcome: at week 24, opioid dose verified through the prescription monitoring system was 113.3 mg morphine equivalent/day in the cannabis group and 97.9 in the waitlist group (difference 15.4; 95% CI −24.4 to 55.3; p = 0.45); pain and its interference with daily life (PEG, 0–10) 5.35 versus 5.30 (difference 0.05; 95% CI −0.46 to 0.57; p = 0.85). No difference in self-reported opioid dose either (−5.6; 95% CI −29.0 to 17.9). The anxiety score was somewhat higher in the cannabis group (difference 3.2; p = 0.047). Participants were not blinded and products were unrestricted; results only in the ClinicalTrials.gov registry (no peer-reviewed publication found in the October 2026 search). Supported by NIDA Side effects: More cannabis use disorder symptoms in the cannabis group (0.54 versus 0.03; difference 0.51; 95% CI 0.30–0.72; p < 0.001); serious adverse events in 7 of 42 and 5 of 45 people (one in the cannabis group was opioid withdrawal); anxiety symptoms as a side effect in 12 versus 4 people | NCT04827992, 2026), PMID 35680252 |
| Abrams 2011 Open-label clinical study without a control group (inpatient, 5 days; drug interaction) | 21 Patients with chronic pain taking long-acting morphine or oxycodone twice a day (US) | Vaporized inhaled cannabis (THC content not in the abstract) | Evening of day 1, 3 times a day on days 2–4, morning of day 5 | 5 days | Total blood levels of morphine and oxycodone did not change significantly with cannabis (registry: geometric mean ratio morphine 0.95, oxycodone 0.94); the peak morphine level fell slightly (0.90). Pain fell by an average of 27% (95% CI 9–46); because there was no control group and no blinding, it is not known how much of this reduction came from cannabis. The opioid dose was not reduced in the study Side effects: No side effects reported in the registry (24 participants) | PMID 22048225, doi:10.1038/clpt.2011.188, NCT00308555 |
| Chou 2026 (AHRQ living review update) Systematic review and meta-analysis (placebo-controlled RCTs only; products grouped by THC:CBD ratio; search up to July 28, 2025; PROSPERO CRD42021229579) | 25 short-term (1–6 months) RCTs, 2303 people (64% neuropathic pain) Adults with chronic pain (mostly neuropathic pain) | Cannabis-based products (THC-dominant, balanced THC:CBD, CBD-dominant; synthetic, purified or extract) | Oral synthetic or purified THC may reduce pain slightly (−0.78/10), and a balanced THC:CBD oral spray probably reduces it slightly (−0.54/10). Among THC products, nabilone reduced pain moderately (−1.59), while dronabinol did not (−0.23). CBD-dominant (low THC:CBD ratio) products may not improve outcomes; CBD alone may not increase side effects. No long-term outcomes. Funded by the US Agency for Healthcare Research and Quality (AHRQ). The 2025 report of the same living review found the evidence insufficient for the effect of cannabis on opioid use Side effects: Moderate or large increase in dizziness, drowsiness and nausea with THC products | PMID 41429020, doi:10.7326/ANNALS-25-03152, PMID 40956916, search April 28, 2025, 29 RCTs and 15 observational studies, oral pure CBD did not reduce pain: 4 RCTs, 334 people, difference 0.40, 95% CI −0.14 to 1.00, moderate certainty, evidence insufficient for its effect on opioid use), PMID 35667066 | ||
| Stockings 2018 Systematic review and meta-analysis (controlled and observational studies; search July 2017) | 104 studies (47 RCTs, 57 observational), 9958 people Non-cancer chronic pain (48 neuropathic, 7 fibromyalgia, 13 MS, 6 visceral pain, 29 mixed or undefined) | Cannabis and cannabinoids (various product types) | In RCTs, at least a 30% reduction in pain occurred in 29.0% with cannabinoids and 25.9% with placebo; 24 people need to be treated for one person to benefit at this level (95% CI 15–61). No difference for a 50% reduction. The difference in pain intensity was about 3 mm on a 100 mm scale (SMD −0.14). No difference in physical and emotional functioning. The authors write that cannabinoids seem unlikely to be highly effective medicines for non-cancer chronic pain Side effects: Any side effect 81.2% versus 66.2%: 1 in every 6 people treated has an additional side effect | PMID 29847469, doi:10.1097/j.pain.0000000000001293 | ||
| Jeddi 2024 Systematic review and network meta-analysis (RCTs only, at least 4 weeks of follow-up; GRADE; search up to March 2021; PROSPERO CRD42020185184) | 90 RCTs, 22,028 people (66 opioid–placebo, 23 cannabis product–placebo, 1 nabilone–dihydrocodeine comparison) Adults with non-cancer chronic pain | Non-inhaled cannabis products (THC:CBD 11, THC 7, CBD 2, CBDV 1 and palmitoylethanolamide 2 studies) and opioids | 28–180 days | No difference or a very small difference in pain between cannabis products and opioids (0.23 cm on a 10 cm scale; 95% credible interval −0.06 to 0.53; low certainty); probably no difference in physical function (moderate certainty). Both reduced pain slightly compared with placebo (moderate certainty for opioids, low or moderate certainty for cannabis products). The comparisons were almost entirely indirect: there was only one study directly comparing a cannabis product with an opioid; the large comparative RCT in chronic low back pain (Meissner 2025) was published after this review. Publicly funded (Canada); the authors reported no conflicts of interest Side effects: Discontinuation due to side effects less common with cannabis products than with opioids (OR 0.55; 95% credible interval 0.36–0.83; moderate certainty) | PMID 38171632, doi:10.1136/bmjopen-2022-068182 | |
| Noori 2021 Systematic review and meta-analysis (RCTs and observational studies; GRADE; part of the BMJ Rapid Recommendations series; PROSPERO CRD42018091098) | 5 RCTs (all in cancer pain) and 12 observational studies Patients with chronic pain taking prescription opioids | Medical cannabis or cannabinoids added to opioids | In RCTs (all of which kept the opioid dose fixed), adding cannabis did not change opioid use (−3.4 mg morphine equivalent; 95% CI −12.7 to 5.8; very low certainty) and did not reduce pain (−0.18 cm/10 cm; high certainty). In 8 observational studies, opioid use fell (−22.5 mg; 95% CI −43.06 to −1.97), but the evidence is very low certainty. The authors write that the opioid-sparing effect is uncertain. Because all the RCTs were done in cancer pain, there was no RCT examining opioid reduction in non-cancer pain Side effects: Adding cannabis probably increased nausea (RR 1.43; 95% CI 1.04–1.96) and vomiting (RR 1.5; 1.01–2.24); no difference in constipation | PMID 34321302, doi:10.1136/bmjopen-2020-047717 | ||
| Zeraatkar 2022 Systematic review and meta-analysis of observational studies (GRADE; part of the BMJ Rapid Recommendations series) | 39 studies, 12,143 adults Patients with chronic pain using medical cannabis or cannabinoids, followed for at least 4 weeks | Medical cannabis and cannabinoids (including palmitoylethanolamide studies) | Side effects are common with long-term use: in 26% of users (95% CI 13.2–41.2), with psychiatric side effects in 13.5%. Serious adverse events, side effects leading to discontinuation, cognitive side effects, accidents and injuries, and dependence and withdrawal each occurred in fewer than 1 in 20 people. Side effects were reported more often with longer follow-up. The evidence is very low certainty; comparative harm data against other treatments such as opioids are insufficient Side effects: Any side effect 26%; psychiatric 13.5%; serious side effects each below 5% | PMID 35926992, doi:10.1136/bmjopen-2021-054282 | ||
| Bialas 2022 Systematic review and meta-analysis of prospective observational studies (at least 26 weeks); search up to December 2021 | 6 studies, 2686 people Non-cancer chronic pain (nociceptive, nociplastic, neuropathic and mixed) | Cannabis-based medicines | 26–52 weeks | With long-term use, pain fell from baseline by an average of 1.75 points (0–10; 95% CI 0.72–2.78); 20.8% of patients reported at least 50% relief. The evidence was very low certainty for all outcomes (no control group). Only 53% of patients completed the study. The authors write that observational data should be interpreted with caution and that their pre-specified 'large effect' criterion was not met Side effects: Discontinuation due to side effects 6.8%; serious adverse events 3.0%; deaths 0.3% | PMID 35467781, doi:10.1002/ejp.1957 | |
| Fink 2026 Systematic review (state-level policy studies; PROSPERO CRD42023416119; search up to October 21, 2025) | 43 studies US states: medical and recreational cannabis laws and opioid outcomes | Cannabis legalization (a policy, not a product) | The effect of cannabis laws on opioid prescriptions varies from study to study; no study found a decrease in non-prescribed opioid use or opioid use disorder after medical cannabis laws. An association between medical cannabis laws and lower opioid death rates was seen only in older studies, not in newer ones. The authors write that legalization should not be considered an effective policy for reducing the opioid epidemic. Population-level data; does not show an opioid-reducing effect in individuals | PMID 42061001, doi:10.1016/j.drugalcdep.2026.113167 | ||
| NICE 2019 (NG144 guideline) National clinical guideline (United Kingdom; systematic evidence review and cost-effectiveness model) | Adults with chronic pain (the guideline also covers nausea, spasticity and epilepsy) | Cannabis-based medicinal products (nabilone, dronabinol, THC, THC + CBD, CBD) | Does not recommend nabilone, dronabinol, THC or the THC + CBD combination for chronic pain; recommends CBD only as part of a clinical trial. Rationale: the average benefit was small (about 0.4 points on a 0–10 scale), the evidence did not show that opioid use fell in people receiving medical cannabis, there was no evidence for CBD alone, and the small benefit did not justify the high cost. Recommends research on CBD in fibromyalgia and treatment-resistant neuropathic pain | PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021), PMID 35107907 | ||
| ACP 2025 (American College of Physicians recommendation) Best practice advice (American College of Physicians Population Health and Medical Science Committee; based on a living systematic review of cannabis and cannabinoids in non-cancer chronic pain and on other reviews) | Adults with non-cancer chronic pain | Cannabis and cannabinoids | Physicians should discuss benefits and harms with patients with non-cancer chronic pain who are considering or using cannabis or cannabinoids; explain to young adults and adolescents, to patients with a current or past substance use disorder, with serious mental illness, or who are frail or at risk of falls, that the harms most likely outweigh the benefits; advise not starting or stopping in pregnancy, breastfeeding or when planning a pregnancy; and advise against inhaled cannabis. There is no general 'use' or 'don't use' recommendation for everyone | PMID 40183677, doi:10.7326/ANNALS-24-03319 | ||
| Ware 2015 (COMPASS) Prospective, multicenter controlled cohort (control group: people with chronic pain who did not use cannabis) | 431 (215 cannabis, 216 control) Non-cancer chronic pain (Canada, 7 clinics); most people in the cannabis group were already using or had previously used cannabis | Standardized herbal cannabis (12.5% THC) | Median 2.5 g/day | 1 year | The primary outcome was safety: the risk of serious adverse events did not differ between groups (adjusted rate ratio 1.08; 95% CI 0.57–2.04); non-serious adverse events were more common in the cannabis group (1.73; 1.41–2.13), most mild or moderate. No difference in lung function, cognitive function or blood tests. Not randomized; cannabis-experienced patients were enrolled Side effects: Non-serious adverse events 73% more common; most mild or moderate | PMID 26385201, doi:10.1016/j.jpain.2015.07.014, ISRCTN19449752 |
| Campbell 2018 (POINT) Prospective national cohort (4 years, annual interviews) | 1514 People with non-cancer chronic pain prescribed opioids (Australia; recruited through pharmacies) | People's own cannabis use; not a medical cannabis program, but cannabis obtained through illegal channels (no product information) | Number of days used in the past month | 4 years | Over 4 years, 24% of participants used cannabis for pain. Cannabis users had greater pain severity (RR 1.14–1.17) and pain interference, lower confidence in coping with pain, and more anxiety. No temporal relationship was found between cannabis use and pain; there is no evidence that cannabis reduced opioid dose or increased opioid discontinuation. Observational; cannabis use was self-reported. Publicly funded | PMID 29976328, doi:10.1016/S2468-2667(18)30110-5 |
| Goedel 2022 Population-based, retrospective individual cohort (medical cannabis registry + prescription monitoring program; comparison with each person's own earlier period) | 5296 people with a medical cannabis license Adults who obtained a medical cannabis license in Rhode Island (US) | Licensed medical cannabis (no product information) | April 2016–March 2019 | Obtaining a license did not change the likelihood of receiving any opioid prescription (OR 0.99; 95% CI 0.94–1.05), a prescription of 50 mg morphine equivalent and above (0.93; 0.84–1.04) or 90 mg and above (0.99; 0.86–1.15). The authors write that a medical cannabis license was not associated with stopping or reducing opioids. Publicly funded (NIH) | PMID 34695720, doi:10.1016/j.drugpo.2021.103502 | |
| Nguyen 2023 Retrospective cohort (New York State prescription monitoring data; comparison of people receiving medical cannabis for more than 30 days versus 30 days or less) | 8165 (4041 longer, 4124 shorter duration) Patients who started medical cannabis for chronic pain while on long-term opioid therapy (US, 2017–2019) | Medical cannabis products in the state program (product details not in the abstract) | 8 months after starting cannabis | Opioid dose fell more in those who received cannabis for longer; the difference in monthly reduction grew with baseline dose: below 50 mg morphine equivalent −1.52 (95% CI −1.67 to −1.37), at 50–90 mg −3.24 (−3.61 to −2.87), at 90 mg and above −9.33 (−9.89 to −8.77) mg/month. The comparison group also consisted of people who received cannabis for a short time; observational, pain was not measured. The authors reported no conflicts of interest | PMID 36716026, doi:10.1001/jamanetworkopen.2022.54573 | |
| Slawek 2026 Prospective cohort (pharmacist-reported medical cannabis dispensing and state prescription monitoring data; marginal structural models) | 204 Adults prescribed opioids for chronic pain who received a new medical cannabis certification in New York (Bronx; mean age 57) | Medical cannabis products in the state program (varying THC and CBD ratios) | 18 months | Daily opioid dose fell on average from 73.3 to 57.4 mg morphine equivalent over 18 months; in months with 30 days of cannabis dispensed, 3.53 mg less opioid a day compared with months with none (95% CI −6.68 to −0.04; p = 0.03): a small difference. Non-prescribed cannabis use was taken into account; not randomized. Funded by NIDA; 1 of the 13 authors is a shareholder and former employee of a cannabis company (Vireo) outside the study | PMID 41359313, doi:10.1001/jamainternmed.2025.6496, NCT04308148, NCT04495725, finished March 2024, result not published as of the October 2026 search) | |
| Fontaine 2026 Population-based cohort (Ontario health data; inverse probability weighted comparison) | 3427 with a cannabis prescription, 12,006 controls Patients aged 66 and over with chronic pain who had not taken opioids in the past year (Canada, 2014–2019) | Authorized cannabis prescription (product information not in the abstract) | 1 year after the prescription | Starting opioid treatment of at least 90 days in the following year was more common among those who received a cannabis prescription (1.84 versus 1.19 per 100 person-years; adjusted RR 1.54; 95% CI 1.07–2.23); significant in men (1.82), not significant in women (1.35). Observational; people who start cannabis may be sicker | PMID 41267332, doi:10.1080/10826084.2025.2586250 | |
| Vozoris 2024 Population-based retrospective cohort (Ontario health data; propensity score matching; comparison: new opioid starters) | 18,863 new nabilone starters and 18,863 matched new opioid starters People aged 12 and over diagnosed with a musculoskeletal condition in the past 3 years (Ontario, Canada) | Nabilone capsules (a synthetic THC-like cannabinoid); comparison: opioids | Not reported (in the abstract) | First 3 months after starting | Compared with opioid starters, nabilone starters had less pneumonia (HR 0.78; 95% CI 0.63–0.96), fewer falls or fractures (0.56; 0.50–0.64) and fewer deaths (0.79; 0.65–0.95), but more mental and behavioral disorders due to substance use (2.23; 1.45–3.43); no difference in traffic accidents. Observational; unmeasured confounders may have affected the results; pain and opioid dose were not measured. The authors warn against widely recommending nabilone in place of opioids because the results are mixed. Funded by the Ontario Ministry of Health; the authors reported no conflicts of interest Side effects: Risk of mental and behavioral disorders due to substance use about 2-fold | PMID 39141203, doi:10.1007/s11606-024-08978-2 |
| Erridge 2026 (UK Medical Cannabis Registry) Prospective patient registry cohort (no comparison group; missing data filled in with multiple imputation) | 3744 Patients whose primary indication was chronic pain and who were prescribed cannabis-based products at a private clinic (United Kingdom) | Dried flower and/or oil (products containing THC and CBD) | Median daily THC 19 mg at baseline, 126.5 mg at month 24; CBD from 15 mg to 20.5 mg | Up to 24 months | All measures improved from baseline (effect size for pain intensity d = 0.57); at month 24, more than half of patients reported a clinically meaningful reduction in pain. Among opioid users, 22.7% had a clinically meaningful reduction in opioid dose (at least 28%) (baseline average 33 mg morphine equivalent/day). However, at month 24 only 35% of patients had pain data, and results were calculated by statistically filling in the missing data; there is no comparison group. 11 of the 12 authors are linked to the company that runs the registry and prescribes the products (Curaleaf) Side effects: 14.4% of patients reported side effects; most mild or moderate | PMID 42885647, doi:10.1002/jcph.70313, PMID 34937477, 190 patients), PMID 37021592, 761 patients), PMID 39545361, 1139 patients) |
| Überall 2026 (CARE, German Pain e-Registry) Retrospective, propensity score–matched two-cohort registry study (no placebo, not randomized) | 968 (484 CBD-dominant extract, 484 THC or dronabinol) Patients aged 65 and over with chronic or treatment-resistant pain (Germany) | CBD-dominant full-spectrum extracts (CBD > THC) or pure THC/dronabinol; the CBD-dominant group also took 16–17 mg of THC a day on average (CBD:THC 2.1:1) | At week 24, an average of 33.5 mg CBD + 16.2 mg THC/day in the CBD-dominant group; 18.6 mg THC/day in the THC group | 24 weeks | Composite outcome (no discontinuation due to side effects and meaningful improvement in pain, function or sleep) 85.7% in the CBD-dominant group, 21.9% in the THC group (p < 0.001). This is not a CBD–placebo comparison: the CBD-dominant group also took around 16 mg of THC a day, and patients were not randomized to treatment. The analysis was funded by an unrestricted grant from a company that sells cannabis products (Stadapharm); 2 of the 4 authors reported receiving fees from this company, and the first author is a manager of the data company that runs the registry Side effects: Patients with drug-related side effects 15.5% versus 35.7%; discontinuation due to side effects 5.6% versus 19.2% | PMID 41821925, doi:10.2147/JPR.S551457, EU PAS EUPAS1000000490 |
| Capano 2020 Prospective, single-arm cohort (no control group) | 131 enrolled; 97 completed Patients aged 30–65 with chronic pain who had been taking opioids for at least 1 year (a private pain clinic) | CBD-rich hemp extract (THC content not in the abstract) | Not reported (in the abstract) | 8 weeks | At 8 weeks, 53% of patients reported reducing or stopping their opioid dose; sleep (PSQI; p = 0.003) and pain interference (PEG; p = 0.006) improved, with no significant change in pain-related disability or mood. No control group and no blinding; the full text could not be read, and the product dose, funding and conflict-of-interest statement could not be verified Side effects: Not reported (in the abstract) | PMID 31711352, doi:10.1080/00325481.2019.1685298 |
Reported side effects
- Pure CBD in the fibromyalgia study: side effects mostly mild and similar between groups (Rasmussen 2026)
- With 200 mg CBD + hydromorphone, 'bad effects' increased (Bergeria 2025)
- THC-containing products: dizziness, drowsiness, nausea (Wang 2021); adverse events 83.3% versus 67.3%, discontinuation due to side effects 17.3% versus 3.5% (VER-01)
- With long-term use (observational studies), about a quarter of users reported side effects; serious side effects occurred in fewer than 1 in 20 people (Zeraatkar 2022). In two studies where cannabis use was assigned by lottery, symptoms of cannabis use disorder increased (Gilman 2022; in opioid users, NCT04827992)
Monitoring done in studies
- Epidiolex label: at 10–20 mg/kg/day, ALT >3× ULN in 13% (placebo 1%); the risk rises markedly with valproate; monitoring at baseline, at months 1, 3 and 6, and after dose changes
- In healthy adults, 5 mg/kg/day gave ALT/AST >3× ULN in 5.6% (placebo 0%) and eosinophilia (Florian 2025, PMID 40622698); 1500 mg/day gave >5× ULN in 31% (Watkins 2021, PMID 33022751)
- Liver enzymes should be monitored when combined with acetaminophen (paracetamol) and other medicines that strain the liver (Pramhas 2023, PMID 38033459)
Who should be careful
- CBD is not an approved medicine for any type of pain
- In patients taking methadone, high-dose CBD (1200 mg) lowered the pain threshold (Costa 2026)
- The expectation that CBD reduces opioid use is not supported by RCTs; the opioid dose should not be reduced on one's own
- In non-prescription products, the content on the label may not match the actual content (Moore 2024)
- When THC-containing products were taken together with opioids, laboratory studies in healthy volunteers found that the opioid's 'liking' and abuse-related effects could increase (Nielsen 2022)
Drug interactions
- Opioids: fentanyl + 400–800 mg CBD, no increase in side effects; hydromorphone + 200 mg CBD, 'bad effects' increased; methadone + 1200 mg CBD, pain threshold fell. Inhaled cannabis did not significantly change total blood levels of morphine and oxycodone (Abrams 2011); in laboratory studies in healthy volunteers, THC could increase the abuse-related effects of opioids (Nielsen 2022). An opioid-reducing effect has not been proven; sedation should be monitored
- CNS depressants (gabapentin, pregabalin, benzodiazepines, alcohol): additive sedation; with Epidiolex, somnolence 32% versus 11%. No direct clinical study of CBD + gabapentinoids has been reported
- NSAIDs: on the label, no significant change in the CYP2C9 substrate tolbutamide; no direct study of CBD + NSAIDs has been reported; no documented significant interaction
- Acetaminophen (paracetamol): in knee OA, enzyme elevations were more common with acetaminophen 3 g + CBD 600 mg; liver enzymes should be monitored
- Warfarin: in a case report, INR rose and the warfarin dose was reduced; INR should be monitored when CBD is started or stopped
- Clopidogrel: the antiplatelet effect may be reduced via CYP2C19 (label); cardiology should be consulted
- DOACs (apixaban, rivaroxaban): no direct data reported; uncertain, should be disclosed and monitored
- Valproate (liver, high risk) and clobazam (sedation 46% versus 16%)
- Tizanidine, theophylline (CYP1A2): the label recommends considering a dose reduction
- Tacrolimus, sirolimus, everolimus, digoxin: monitoring or dose reduction (label)
- Strong inducers such as rifampin: CBD levels fall by ~32%
- Note: label data come from high-dose pharmaceutical CBD; with non-prescription products the size of an interaction may differ, but its direction should be assumed to be the same
Abbreviations: RCT, randomized controlled trial (a study in which participants are assigned to groups by chance); placebo, an inactive substance; SMD, OR and RR, effect measures used in analyses that pool studies; CYP, liver enzymes that break down medicines.
If you are considering CBD
- You can talk with your doctor or a pain specialist about the cause of your chronic pain and the treatment options that suit you.
- Do not reduce or stop your opioid painkillers on your own; CBD has not been shown to replace these medicines.
- If you take methadone, an opioid, a sleep medicine or a blood thinner, talk about interactions with your doctor and pharmacist.
- In non-prescription products, the content on the label may not match the actual content; look for an independent laboratory certificate of analysis.
Choose your age group, medicines and situation to prepare a short summary you can take to your doctor. Nothing you enter is sent anywhere.
Bottom line
Despite many studies, pure CBD has not been shown to be better than a dummy pill for chronic pain; there is also no good evidence that it reduces the need for opioids. Living with pain for a long time is exhausting; building a treatment plan that suits you together with your doctor is the most solid path.
Frequently asked questions
Does CBD oil work for chronic pain?
There are many well-designed studies on this, and the results point largely in the same direction: in 15 of 16 studies that used pharmaceutical-grade pure CBD, CBD was no better than a dummy pill (placebo). The evidence is moderate and does not support CBD being helpful for chronic pain.
Can I lower the dose of my opioid painkillers with CBD?
Well-designed studies have not shown that CBD reduces the need for opioids; the only controlled CBD study in patients taking opioids could be completed with just 6 people. In a study where cannabis use was assigned by lottery to people taking opioids, the opioid dose also did not go down over 24 weeks. Most studies reporting lower opioid use are observational studies without a comparison group; in large studies looking at prescription records, a decrease was either not seen at all or was small. In people taking methadone, high-dose CBD increased sensitivity to pain. Do not change your opioid dose on your own.
Does CBD help with fibromyalgia?
In a study that followed 200 people with fibromyalgia for 24 weeks, pain went down slightly more in the placebo group than in the CBD group. In other words, this study did not find CBD helpful for fibromyalgia pain.
Are THC-containing products more effective for chronic pain?
THC-containing products taken by mouth brought a small or very small improvement in pain; on the other hand, dizziness, drowsiness and nausea increased. Expert organizations also differ: one guideline gives a weak recommendation, while the international pain association does not support general use, and the UK's national guideline also does not recommend them for chronic pain; a guideline prepared in Canada gives a strong recommendation, but a cannabis company supported its preparation and it also takes studies without a comparison group into account; the US physicians' organization ACP stresses that in young adults and adolescents, in people with a substance use disorder or serious mental illness, and in frail patients, the harms most likely outweigh the benefits.
Can CBD oil be obtained with a prescription for chronic pain in Turkey?
In Turkey, products derived from cannabis are regulated by the Kenevirden Elde Edilen Ürünlere Dair Yönetmelik (Regulation on Products Derived from Hemp) dated January 31, 2026. These products, including CBD, can be sold only in pharmacies. Those classed as medicines and health products are dispensed with a prescription; the regulation does not state a prescription requirement for support products and cosmetics with a THC content of at most 0.3%. As of October 2026, there is no approved (licensed) CBD medicine in Turkey. If you are thinking of using it, talk to your doctor first.
Patient registries say pain goes down with cannabis; why isn't that enough?
These registries have no comparison group: pain can also ease on its own over time, people who are not satisfied with the treatment drop out of follow-up, and the expectation effect (placebo effect) is strong in pain. For example, in the large UK registry, data were available for only a third of patients at the end of 2 years. In placebo-controlled studies the difference is much smaller, and reviews that pooled these registries rated the evidence as very low certainty.
References
Show 47 references
- Rasmussen 2026. Double-blind, placebo-controlled, single-center RCT. PMID 40846590, doi:10.1016/j.ard.2025.07.008, NCT04729179, no results in the registry)
- Bergeria 2025. Within-subject, double-blind, double-dummy RCT. PMID 40839659, doi:10.1097/j.pain.0000000000003561
- Costa 2026. Crossover, double-blind, placebo-controlled RCT. PMID 42162267, doi:10.1038/s41386-026-02443-w, NCT04587791, PMID 41496743, 7 people with chronic pain on methadone or buprenorphine, 400–1200 mg CBD, no significant main effect on pain sensitivity, an interaction with medication type, CBD well tolerated)
- Anelli 2026 (DREAMLAND). Single-center, triple-blind, placebo-controlled parallel RCT; stopped at an interim analysis. PMID 42261989, doi:10.1177/25785125251413989
- Reeve 2026. Single-center, placebo-controlled RCT (2:1 randomization); in the registry only participants were blinded, according to the publication assessors were also blinded. PMID 42016900, doi:10.1159/000551040, NCT04298554, the registered primary outcome was change in pain from baseline at weeks 3, 7 and 11, the published primary outcome was pain at month 1, no difference under either definition, no results in the registry), PMC13095194, the same study is also in the site's jaw joint and teeth clenching table
- Manini 2015. Crossover, double-blind, placebo-controlled. PMID 25748562, doi:10.1097/ADM.0000000000000118
- Karst 2025 (VER-01, placebo-controlled). Phase 3, double-blind, placebo-controlled RCT. PMID 41023483, doi:10.1038/s41591-025-03977-0, NCT04940741, the RCT comparing the same product with opioids is a separate row in the table (Meissner 2025)
- Moore 2024 (J Pain). Systematic review (pure CBD pain RCTs after IASP). PMID 37863344, doi:10.1016/j.jpain.2023.10.009
- Fisher 2021 (IASP systematic review). Systematic review (RCTs; IASP task force; GRADE). PMID 32804836, doi:10.1097/j.pain.0000000000001929
- Wang 2021. Systematic review and meta-analysis (32 RCTs). PMID 34497047, doi:10.1136/bmj.n1034
- Busse 2021 (BMJ Rapid Recommendation). Clinical practice guideline. PMID 34497062, doi:10.1136/bmj.n2040
- Nielsen 2022. Systematic review and meta-analysis (preclinical + clinical). PMID 35459926, doi:10.1038/s41386-022-01322-4
- Moore 2024 (Pain). Publication bias analysis. PMID 38227560, doi:10.1097/j.pain.0000000000003140
- IASP 2021 position statement. Task force position statement. PMID 33729207, doi:10.1097/j.pain.0000000000002265, www.iasp-pain.org
- Notcutt 2004. Open-label run-in period followed by randomized, double-blind, placebo-controlled crossover 'N-of-1' (single-patient) trials. PMID 15096238, doi:10.1111/j.1365-2044.2004.03674.x
- Pinsger 2006. Double-blind, placebo-controlled crossover pilot RCT (2 × 4-week drug periods) followed by a 16-week period in which patients chose their own medicine. PMID 16855921, doi:10.1007/s00508-006-0611-4
- Narang 2008. Two phases: phase 1 randomized, double-blind, placebo-controlled, single-dose crossover RCT (3 visits × 8 hours); phase 2 open-label extension with dose adjustment. PMID 18088560, doi:10.1016/j.jpain.2007.10.018, NCT00153192, PMID 24281276, 10 and 20 mg dronabinol increased mind-altering effects more than placebo on 4 of 5 subscales, with peak effects similar to smoked marijuana)
- de Vries 2016. Randomized, double-blind, double-dummy, active placebo-controlled, single-dose crossover RCT. PMID 26505163, doi:10.1111/bcp.12811, NCT01318369
- de Vries 2017. Phase 2, randomized, double-blind, placebo-controlled parallel RCT. PMID 27720917, doi:10.1016/j.cgh.2016.09.147, NCT01562483
- Abrams 2020. Pilot, randomized, double-blind, placebo-controlled crossover RCT (inpatient, 2 × 5 days). PMID 32678452, doi:10.1001/jamanetworkopen.2020.10874, NCT01771731
- Kliuk-Ben Bassat 2023. Randomized, double-blind, three-arm crossover feasibility RCT (primary outcome safety). PMID 37007688, doi:10.1093/ckj/sfac275
- Gilman 2022. Pragmatic RCT (getting a medical cannabis card immediately or after 12 weeks; 2:1 randomization; participants not blinded, only assessors blinded). PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, 12 weeks, cannabis use frequency rose in those who got the card, reported sleep quality was better on days of use, no improvement in pain or depressive symptoms)
- Meissner 2025 (VER-01, comparison with opioids). Phase 3, multicenter, randomized, open-label (not blinded) parallel RCT; comparison: opioid. PMID 41028525, doi:10.1007/s40122-025-00773-z, NCT05610813, EudraCT 2022-001358-41
- NCT04527003 (endometriosis, registry results). Randomized, double-blind, placebo-controlled three-arm pilot RCT; ended early because patients could not be recruited; no peer-reviewed publication. NCT04527003, 2025, no publication found in the October 2026 search)
- Chesterman 2025. Three-arm, randomized, placebo-controlled feasibility RCT. PMID 41005282, doi:10.1016/j.ctcp.2025.102023
- NCT04760613 (CBD in opioid users, registry results). Phase 1/2, randomized, double-blind, placebo-controlled pilot RCT; no peer-reviewed publication. NCT04760613, 2024, no publication found in the October 2026 search)
- NCT04827992 (cannabis in opioid users, registry results). Pragmatic, randomized, waitlist-controlled parallel study (only outcome assessors blinded); both groups attended a weekly opioid tapering support group for 24 weeks; no peer-reviewed publication. NCT04827992, 2026), PMID 35680252
- Abrams 2011. Open-label clinical study without a control group (inpatient, 5 days; drug interaction). PMID 22048225, doi:10.1038/clpt.2011.188, NCT00308555
- Chou 2026 (AHRQ living review update). Systematic review and meta-analysis (placebo-controlled RCTs only; products grouped by THC:CBD ratio; search up to July 28, 2025; PROSPERO CRD42021229579). PMID 41429020, doi:10.7326/ANNALS-25-03152, PMID 40956916, search April 28, 2025, 29 RCTs and 15 observational studies, oral pure CBD did not reduce pain: 4 RCTs, 334 people, difference 0.40, 95% CI −0.14 to 1.00, moderate certainty, evidence insufficient for its effect on opioid use), PMID 35667066
- Stockings 2018. Systematic review and meta-analysis (controlled and observational studies; search July 2017). PMID 29847469, doi:10.1097/j.pain.0000000000001293
- Jeddi 2024. Systematic review and network meta-analysis (RCTs only, at least 4 weeks of follow-up; GRADE; search up to March 2021; PROSPERO CRD42020185184). PMID 38171632, doi:10.1136/bmjopen-2022-068182
- Noori 2021. Systematic review and meta-analysis (RCTs and observational studies; GRADE; part of the BMJ Rapid Recommendations series; PROSPERO CRD42018091098). PMID 34321302, doi:10.1136/bmjopen-2020-047717
- Zeraatkar 2022. Systematic review and meta-analysis of observational studies (GRADE; part of the BMJ Rapid Recommendations series). PMID 35926992, doi:10.1136/bmjopen-2021-054282
- Bialas 2022. Systematic review and meta-analysis of prospective observational studies (at least 26 weeks); search up to December 2021. PMID 35467781, doi:10.1002/ejp.1957
- Fink 2026. Systematic review (state-level policy studies; PROSPERO CRD42023416119; search up to October 21, 2025). PMID 42061001, doi:10.1016/j.drugalcdep.2026.113167
- NICE 2019 (NG144 guideline). National clinical guideline (United Kingdom; systematic evidence review and cost-effectiveness model). PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021), PMID 35107907
- ACP 2025 (American College of Physicians recommendation). Best practice advice (American College of Physicians Population Health and Medical Science Committee; based on a living systematic review of cannabis and cannabinoids in non-cancer chronic pain and on other reviews). PMID 40183677, doi:10.7326/ANNALS-24-03319
- Ware 2015 (COMPASS). Prospective, multicenter controlled cohort (control group: people with chronic pain who did not use cannabis). PMID 26385201, doi:10.1016/j.jpain.2015.07.014, ISRCTN19449752
- Campbell 2018 (POINT). Prospective national cohort (4 years, annual interviews). PMID 29976328, doi:10.1016/S2468-2667(18)30110-5
- Goedel 2022. Population-based, retrospective individual cohort (medical cannabis registry + prescription monitoring program; comparison with each person's own earlier period). PMID 34695720, doi:10.1016/j.drugpo.2021.103502
- Nguyen 2023. Retrospective cohort (New York State prescription monitoring data; comparison of people receiving medical cannabis for more than 30 days versus 30 days or less). PMID 36716026, doi:10.1001/jamanetworkopen.2022.54573
- Slawek 2026. Prospective cohort (pharmacist-reported medical cannabis dispensing and state prescription monitoring data; marginal structural models). PMID 41359313, doi:10.1001/jamainternmed.2025.6496, NCT04308148, NCT04495725, finished March 2024, result not published as of the October 2026 search)
- Fontaine 2026. Population-based cohort (Ontario health data; inverse probability weighted comparison). PMID 41267332, doi:10.1080/10826084.2025.2586250
- Vozoris 2024. Population-based retrospective cohort (Ontario health data; propensity score matching; comparison: new opioid starters). PMID 39141203, doi:10.1007/s11606-024-08978-2
- Erridge 2026 (UK Medical Cannabis Registry). Prospective patient registry cohort (no comparison group; missing data filled in with multiple imputation). PMID 42885647, doi:10.1002/jcph.70313, PMID 34937477, 190 patients), PMID 37021592, 761 patients), PMID 39545361, 1139 patients)
- Überall 2026 (CARE, German Pain e-Registry). Retrospective, propensity score–matched two-cohort registry study (no placebo, not randomized). PMID 41821925, doi:10.2147/JPR.S551457, EU PAS EUPAS1000000490
- Capano 2020. Prospective, single-arm cohort (no control group). PMID 31711352, doi:10.1080/00325481.2019.1685298
Points that could not be verified from the full text
- Rasmussen 2026 (titration, THC content) was read from the abstract only. Of the studies added in the October 2026 search, Notcutt 2004, Pinsger 2006 (in German), Narang 2008, de Vries 2016, de Vries 2017, Abrams 2011, Chesterman 2025, Capano 2020, Ware 2015, Fontaine 2026 and Vozoris 2024, the Chou 2026, Stockings 2018 and Bialas 2022 reviews, and the ACP 2025 recommendation were read from the abstract only; the full text of the AHRQ 2025 report was not read; the results of NCT04527003, NCT04760613 and NCT04827992 were read only from the ClinicalTrials.gov registry; Khatib 2026 was read from the abstract only (the full text requires a subscription; the product, dose and THC content used are not in the abstract; the abstract gives the enrollment period as 2015–2024 while stating that 638 patients completed 10 years of follow-up, so how the follow-up period was calculated could not be verified); the full text of CADTH's 2024 nabilone review could not be opened (bot verification), and its description comes from its abstract on PubMed
- Studies completed as of October 2026 but whose results have not been published or posted to the registry: a dose–response study of a THC-dominant extract in chronic low back pain (NCT06475001, 652 people, finished in July 2025), a study comparing cannabis with oxycodone in back and neck pain (NCT02892591, 33 people, 2023), THC and CBD in chronic widespread pain (NCT03215940, 53 people, 2024), CBD in chronic pain (NCT04044729, 24 people, 2024), an RCT of discounted cannabis coupons in opioid users (NCT04495725, 270 people, 2024; sponsored by a cannabis company), a pilot RCT of CBD and THC + CBD oil in chronic pain (NCT05351905, 51 people, January 2026), and a 161-person cannabis oil RCT that the sponsor stopped in 2019 (NCT03337503)
- Ongoing studies as of October 2026: CBD in US veterans (NCT06213233, 468 people), dronabinol (NCT05519111) and CBD (NCT06930703) in sickle cell disease, oral cannabis in spinal pain (NCT05052541), dronabinol in low back pain (NCT06454669), a THC-dominant extract in radicular pain from the lower back (NCT06956014), CBD in endometriosis and gynecological pain (NCT06477406, NCT07728695)
- In the CBD study in patients with radicular pain taking opioids (NCT04760613), the registry does not say whether the product was pure CBD or an extract; in Capano 2020 the CBD dose, THC content and funding could not be read; the registry results of Meissner 2025 and Karst 2025 have not been posted to ClinicalTrials.gov
Trusted sources from around the world
Show 1 reference
- Cochrane: Cannabis-based medicines for chronic nerve painCochrane, English, January 2026
A plain-language summary of an independent systematic review: benefits and risks, and the certainty of the evidence.
These sources sell no products. All trusted sources
Research history
Here we record what changed on this page, when and why, with dates. The newest change is at the top.
October 2026 additional review: sources found for this page in the searches of other topics were read and worked into the page. The number of people in the medical cannabis card study (Gilman 2022) was corrected (269 people randomized, 186 analyzed), and the daily survey analysis of the same trial was added; for the CBD study in patients with chronic pain on methadone treatment (Costa 2026), it was noted that the primary outcomes in the registry differed from those in the article, that the manufacturer supplied the product, and the registry number was added. Two suggestions were reviewed and not added to the table: a study measuring the effect of THC on experimental pain in people on methadone treatment (participants were not selected for chronic pain), and a 2020 meta-analysis that overlaps with the more recent reviews in the table. The conclusion and the strength of evidence did not change.
In October 2026, PubMed, Cochrane, ClinicalTrials.gov and Europe PMC were searched systematically; 33 studies were added: 13 randomized studies in non-cancer chronic pain (nabilone, dronabinol, purified THC, vaporized inhaled cannabis, THC:CBD oil, two pragmatic studies in which cannabis use was assigned by lottery, and an open-label study comparing a THC-dominant extract with opioids in chronic low back pain; including three studies with results only in the registry: CBD in endometriosis and in opioid users, and cannabis in opioid users), 7 systematic reviews (including the 2026 update from the US Agency for Healthcare Research and Quality and reviews on opioid reduction, long-term safety and comparisons of cannabis with opioids), the UK's national guideline (NICE), the American College of Physicians' (ACP) 2025 recommendation, and 11 observational or uncontrolled studies, including studies that measured opioid use through prescription records. In the topic text, the effect on chronic pain and lowering the opioid dose were described separately, a transparency sentence was added, and a reader-visible reference to an internal file was removed. In existing rows: the chronic low back pain study's withdrawal phase with a negative result and its company ties, the product type of two reviews ('mixed,' because they pooled more than one product), the number of people in one review, and the laboratory and observational findings of the opioid reduction review were added; the fibromyalgia study was aligned with its row on that topic. The conclusion and the strength of evidence did not change.
Related studies: Notcutt 2004, published May 2004 (PMID 15096238, doi:10.1111/j.1365-2044.2004.03674.x); Pinsger 2006, published June 2006 (PMID 16855921, doi:10.1007/s00508-006-0611-4); Narang 2008, published March 2008 (online December 2007) (PMID 18088560, doi:10.1016/j.jpain.2007.10.018, NCT00153192, PMID 24281276, 10 and 20 mg dronabinol increased mind-altering effects more than placebo on 4 of 5 subscales, with peak effects similar to smoked marijuana)); de Vries 2016, published March 2016 (online January 2016) (PMID 26505163, doi:10.1111/bcp.12811, NCT01318369); de Vries 2017, published July 2017 (online October 2016) (PMID 27720917, doi:10.1016/j.cgh.2016.09.147, NCT01562483); Abrams 2020, published July 1, 2020 (PMID 32678452, doi:10.1001/jamanetworkopen.2020.10874, NCT01771731); Kliuk-Ben Bassat 2023, published April 2023 (online December 2022) (PMID 37007688, doi:10.1093/ckj/sfac275); Gilman 2022, published March 1, 2022 (PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, 12 weeks, cannabis use frequency rose in those who got the card, reported sleep quality was better on days of use, no improvement in pain or depressive symptoms)); Meissner 2025 (VER-01, comparison with opioids), published December 2025 (online September 30, 2025) (PMID 41028525, doi:10.1007/s40122-025-00773-z, NCT05610813, EudraCT 2022-001358-41); NCT04527003 (endometriosis, registry results), published April 4, 2025 (registry results) (NCT04527003, 2025, no publication found in the October 2026 search)); Chesterman 2025, published November 2025 (online September 23, 2025) (PMID 41005282, doi:10.1016/j.ctcp.2025.102023); NCT04760613 (CBD in opioid users, registry results), published September 19, 2024 (registry results) (NCT04760613, 2024, no publication found in the October 2026 search)); Abrams 2011, published December 2011 (online November 2011) (PMID 22048225, doi:10.1038/clpt.2011.188, NCT00308555); Chou 2026 (AHRQ living review update), published February 2026 (online December 23, 2025) (PMID 41429020, doi:10.7326/ANNALS-25-03152, PMID 40956916, search April 28, 2025, 29 RCTs and 15 observational studies, oral pure CBD did not reduce pain: 4 RCTs, 334 people, difference 0.40, 95% CI −0.14 to 1.00, moderate certainty, evidence insufficient for its effect on opioid use), PMID 35667066); Stockings 2018, published October 2018 (PMID 29847469, doi:10.1097/j.pain.0000000000001293); Noori 2021, published July 28, 2021 (PMID 34321302, doi:10.1136/bmjopen-2020-047717); Zeraatkar 2022, published August 4, 2022 (PMID 35926992, doi:10.1136/bmjopen-2021-054282); Bialas 2022, published July 2022 (online May 2022) (PMID 35467781, doi:10.1002/ejp.1957); Fink 2026, published July 1, 2026 (online April 17, 2026) (PMID 42061001, doi:10.1016/j.drugalcdep.2026.113167); NICE 2019 (NG144 guideline), published November 11, 2019 (updated March 22, 2021) (PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021), PMID 35107907); Ware 2015 (COMPASS), published December 2015 (online September 2015) (PMID 26385201, doi:10.1016/j.jpain.2015.07.014, ISRCTN19449752); Campbell 2018 (POINT), published July 2018 (PMID 29976328, doi:10.1016/S2468-2667(18)30110-5); Goedel 2022, published February 2022 (online October 2021) (PMID 34695720, doi:10.1016/j.drugpo.2021.103502); Nguyen 2023, published January 3, 2023 (PMID 36716026, doi:10.1001/jamanetworkopen.2022.54573); Slawek 2026, published February 1, 2026 (PMID 41359313, doi:10.1001/jamainternmed.2025.6496, NCT04308148, NCT04495725, finished March 2024, result not published as of the October 2026 search)); Fontaine 2026, published 2026 (PMID 41267332, doi:10.1080/10826084.2025.2586250); Erridge 2026 (UK Medical Cannabis Registry), published October 2026 (PMID 42885647, doi:10.1002/jcph.70313, PMID 34937477, 190 patients), PMID 37021592, 761 patients), PMID 39545361, 1139 patients)); Überall 2026 (CARE, German Pain e-Registry), published 2026 (PMID 41821925, doi:10.2147/JPR.S551457, EU PAS EUPAS1000000490); Capano 2020, published January 2020 (online November 2019) (PMID 31711352, doi:10.1080/00325481.2019.1685298); NCT04827992 (cannabis in opioid users, registry results), published June 24, 2026 (registry results) (NCT04827992, 2026), PMID 35680252); Jeddi 2024, published January 3, 2024 (PMID 38171632, doi:10.1136/bmjopen-2022-068182); ACP 2025 (American College of Physicians recommendation), published May 2025 (online April 4, 2025) (PMID 40183677, doi:10.7326/ANNALS-24-03319); Vozoris 2024, published November 2024 (online August 14, 2024) (PMID 39141203, doi:10.1007/s11606-024-08978-2)
The names of the finding labels were simplified: on this page the "No benefit seen" label became "No effect found." The assessment did not change.
Older changes (3)
PubMed and ClinicalTrials.gov were searched for newly published and previously missed clinical studies. 2 studies added: Anelli 2026 (DREAMLAND) and Reeve 2026. The conclusion and the strength of evidence did not change.
Related studies: Anelli 2026 (DREAMLAND), published January 13, 2026 (PMID 42261989, doi:10.1177/25785125251413989); Reeve 2026, published February 19, 2026 (PMID 42016900, doi:10.1159/000551040, NCT04298554, the registered primary outcome was change in pain from baseline at weeks 3, 7 and 11, the published primary outcome was pain at month 1, no difference under either definition, no results in the registry), PMC13095194, the same study is also in the site's jaw joint and teeth clenching table)
The full texts of the studies were reread and the information on the page was checked against its sources. Corrected: participant numbers, doses, products and dose-increase details in the study table. Points that could not be verified from the full text went down from 2 items to 1 item. The year of 2 publications named on the page was corrected to the journal's print year instead of the online publication year. The conclusion and the strength of evidence did not change.
Page published. This first review examined 12 studies.